Maintenance and cure of the L5178Y murine tumor-dormant state by interleukin 2: in vivo and in vitro effects.
We studied the antitumor effects of recombinant human interleukin 2 (HuIL-2) in DBA/2 mice which harbor L5178Y lymphoma cells in a tumor-dormant state in the peritoneal cavity and in peritoneal cell (PC) cultures prepared from such mice. Intraperitoneal injection of 10,000 to 100,000 units of HuIL-2/day for 10 days eliminated tumor cells from 30-45% of the mice, whereas no mice became tumor-free in the phosphate-buffered saline-treated control group. In vitro, as little as 10 units/well HuIL-2 failed to stimulate cytotoxic activity in PC from normal mice. HuIL-2 directly stimulated antitumor cytotoxic activity in nonadherent but not in adherent PC cultures from tumor-dormant mice; however, treatment of whole PC from tumor-dormant mice with HuIL-2 resulted in the development of antitumor cytotoxic activity in the adherent PC population which were derived from such cultures. This suggests that the HuIL-2-treated nonadherent PC contributed to the cytotoxic activation of the adherent PC. Flow cytometric analysis of the PC from tumor-dormant mice revealed a polyclonal expansion of T-lymphocytes. Lyt-1+, Lyt-2+, and L3T4+ lymphocytes were all required for HuIL-2 to induce antitumor cytotoxic activity.
Liu
C M
CM
Department of Pathology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Suzuki
Y
Y
Chen
L P
LP
Okayasu
T
T
Calkins
C E
CE
Wheelock
E F
EF
D000818:Animals; D002448:Cell Adhesion; D005260:Female; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D012965:Sodium Chloride / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007376:Interleukin-2; D012965:Sodium Chloride